Photodynamic therapy in the treatment of the right buccal mucosa verrucous carcinoma: a case report and literature review / 口腔疾病防治

Objective@#To explore the photodynamic treatment method and therapeutic effect of oral verrucous carcinoma and to provide a reference for the clinic.@*Methods@#This study follows the requirements of medical ethics. This paper summarized the photodynamic treatment of an oral verrucous carcinoma with a diameter of approximately 2.5 cm in the right buccal mucosa and retrospectively analyzed the characteristics and treatment of oral verrucous carcinoma and the photodynamic treatment of potential malignant lesions of the oral mucosa through a review of the literature.@*Results@#After four rounds of photodynamic therapy, the size of the right buccal lesion was significantly reduced. After 6 months of follow-up, the white verrucous hyperplasia of the right buccal mucosa had completely subsided, and there was no obvious scar formation. Three years after treatment, there was no recurrence of the lesion in the right buccal mucosa and no obvious scar formation in the treated area. The degree of mouth opening was 3 fingers, and there was no lymph node enlargement in the bilateral submandibular, submental or neck. The literature review shows that oral verrucous carcinoma is a rare subtype of squamous cell carcinoma with the characteristics and biological behaviors of slow growth, low malignancy, and rare metastasis. Surgery is the preferred treatment, but there are some limitations. Photodynamic therapy is a minimally invasive, repeatable treatment with mild adverse reactions. In recent years, photodynamic therapy has been gradually applied for the treatment of potential malignant disorders of the oral mucosa and early oral squamous cell carcinoma and has achieved positive results, but it has not been reported for the treatment of oral verrucous cancer@*Conclusion@#Photodynamic therapy is a new option for nonsurgical resection of oral verrucous carcinoma.

Synthesis and biological activities of chlorin e6-based conjugate of fluorouracil as dual-mode antitumor photosensitizer / 药学实践杂志

Objective To design and synthesize the conjugate (compound 1) of chlorin e6 (compound 3) with fluorouracil (5-Fu) as novel pH-responsive dual-mode antitumor photosensitizer by acyl hydrazone bond coupling, based on literature reports that combination of 5-Fu and photosensitizer possess synergistic anti-tumor effect, and investigate its photodynamic antitumor activity and mechanism. Methods Lead compound 3 was obtained by alkali degradation with 25% KOH-CH3OH on pheophorbide a (compound 4) which was prepared through acid hydrolysis of chlorophyll a in crude chlorophyll extracts from silkworm excrement. Reflux reaction of 5-Fu with P2S5 in pyridine formed crude 4-thio-5-fluorouracil which was followed to react with hydrazine hydrate (N2H4·H2O) in CH3OH to give 5-fluorouracil-4-hydrazone (compound 2). Then, treatment of compound 3 i.e. acid alkali degradation product of chlorophyll a in silkworm excrement with EDC·HCl generated its 171- and 152 cyclic anhydride which was followed to directly react with intermediate compound 2 to successfully get title compound 1. In addition, its pH-responsive 5-Fu release and photodynamic antitumor activity and their mechanisms in vitro were investigated. Results Compound 1 could responsively release 5-Fu at pH 5.0, with a cumulative release rate of 60.3% within 24 h. It exhibited much higher phototoxicity against melanoma B16-F10 and liver cancer HepG2 cells than talaporfin and its precursor compound 3, with IC50 value being 0.73 μmol/L for B16-F10 cells and 0.90 μmol/L for HepG2 cells, respectively. Upon light irradiation, it also could significantly induce cell apoptosis and intracellular ROS level and block cell cycle in S phase. Its structure was confirmed by UV, 1H-NMR, ESI-MS and elemental analysis data. Conclusion The conjugate compound 1 of compound 3 and 5-Fu has the advantages of strong PDT anticancer activity, high therapeutic index (i.e. dark toxicity/phototoxicity ratio) and responsively release 5-Fu at pH 5.0 etc. which shows “unimolecular” dual antitumor effects of PDT and chemotherapy and is worthy of further research and development.

Clinical application progress on the diode laser in nonsurgical periodontal treatment / 口腔疾病防治

@#Chronic periodontitis is a chronic inflammatory disease caused by plaque microorganisms, and removal of plaque and calculus is the gold standard for nonsurgical periodontal treatment. However, complete debridement is difficult, especially in some complex anatomical sites. Excessive scaling may result in the loss of healthy cementum and lead to dental hypersensitivity. Studies have shown that a diode laser can exhibit the best performance in an environment with blood because its wavelengths (630-1 064 nm) are close to the absorption peaks of heme and melanin and they have broad application prospects in the oral field. In nonsurgical periodontal treatment, diode lasers have three treatment modes: soft diode laser, antimicrobial photodynamic therapy and low-level laser therapy, which can be used alone or in combination. Although diode lasers cannot replace mechanical treatment to remove calculus, they can remove infected periodontal pocket epithelium, change the microcirculation to promote wound healing, reduce bleeding and relieve pain through photothermal effects and biological stimulation. The effect of diode laser treatment depends on the treatment dose. It is necessary to precisely control the output intensity and control the irradiation time to avoid thermal damage to the tissue. In the future, extensive research at the molecular level is needed to reveal the tissue response. At the same time, more high-quality, large-sample randomized controlled trials are needed to standardize the use of lasers for different stages and grades of periodontitis.

Application progress of ROS-responsive liposomes in anti-tumor research / 药学实践杂志

Reactive oxygen species（ROS） responsive liposomes are prepared based on the high level of ROS expression in the tumor microenvironment, enabling precise drug delivery to the tumor site. With the addition of photosensitizer, the controllability of drugs in liposomes can be further enhanced.

Recent progress in delivery systems for photosensitizers and anti-cancer photodynamic therapy / 药学学报

Photodynamic therapy (PDT) is a new modality for cancer therapy, which has been used in the clinical treatment for various tumors, such as skin cancer, bladder cancer and prostate cancer. Most photosensitizers have the disadvantages of hydrophobic, low bioavailability and the limited tumor targeting ability. The nanoscale delivery systems can improve the solubility of photosensitizers and enhance their accumulation at the tumor sites. The multifunctional nano-delivery systems are prepared in combination with other anti-tumor drugs to enhance the anti-tumor effect. In addition to addressing the issues of poor solubility and the insufficient tumor targeting ability, the nanoscale delivery systems need to improve the pharmacokinetic properties of photosensitizers, facilitating their rapid accumulation at the tumor sites and quick elimination in vivo, and reducing the skin phototoxicity. This review summarizes the recent clinical application of PDT of cancer, the development of photosensitizers, the delivery systems for photosensitizers and the combinatorial application with other therapeutic methods. The goal is to present an understanding of knowledge on the design of new types of photosensitizers and its clinical application in PDT of cancer.

Preliminary research on metalized phthalocyanines synthesis. Evaluation as potential photosensitizer in photodynamic therapy

SUMMARY Introduction: Phthalocyanines are porphyrin-based dyes. They have plenty applications in different fields, including biomedical and chemical research. From a chemical point of view, Phthalocyanines are macrocyclictetraaza compounds, which mainly are made up of isoindol groups that confer aromaticity and planarity on Phthalocyanine structure. Unlike other kinds of porphyrin compounds, Phthalocyanine structure is able to chelate a lot of metals, which more often contribute to their huge variety of functions, including ROS generation, fluorescence, absorption spectra, and others. Aim: To evaluate phthalocyanines compounds owing their excellent photochemical and pharmaceutical properties that explain their wide use at the clinical and medical level. Methodology: We have carried out a meticulous search for scientific works related to the subject between April 2020 and April 2021, the most of them were written in English. As a result, we can say that, for studying Phthalocyanines' properties, the work can be separated into two issues: synthesis of the metalized phthalocyanines and photochemical and photobiological properties. Results: Phthalocyanines have plenty properties that are desirable to biomedical and pharmaceutical research. Because of their photochemical and photobiological properties, as well as ROS generation, Phthalocyanines are one of the photosenstitizers most widely used in photodynamic therapy. They also have antibacterial, antiviral and anticancer activities. In this sense, Phthalocyanine synthesis and in vitro studies are a very important scientific issue.

Introducción: las ftalocianinas son tintes porfirínicos. Tienen muchas aplicaciones en diferentes campos, incluida la investigación biomédica y química. Desde el punto de vista químico, las ftalocianinas son compuestos macrocíclicos de tetraaza. Se componen principalmente de grupos isoindol que confieren aromaticidad y planaridad a la estructura de la ftalocianina. Esta última es capaz de quelar muchos metales, que con mayor frecuencia contribuyen a su gran variedad de funciones, incluida la generación de EROS, la fluorescencia, los espectros de absorción y otros. Objetivo: evaluar algunos derivados de ftalocianinas gracias a las excelentes propiedades fotoquímicas y farmacéuticas que explican su amplio uso a nivel clínico y médico. Metodología: hemos realizado una búsqueda minuciosa de trabajos científicos relacionados con el tema entre abril de 2020 y abril de 2021, la mayoría de ellos escritos en inglés. Como resultado, podemos decir que, para estudiar las propiedades de las ftalocianinas, el trabajo se puede dividir en dos temas: síntesis de las ftalocianinas metalizadas y propiedades fotoquímicas y ffotobiológicas. Resultados: las ftalocianinas tienen muchas propiedades que son deseables para la investigación biomédica y farmacéutica. Por sus propiedades fotoquímicas y fotobiológicas, así como por la generación de EROS, las ftalocianinas son uno de los fotosensibilizadores más utilizados en terapia fotodinámica. También tienen actividades antibacterianas, antivirales y anticancerígenas. En este sentido, la síntesis de ftalocianina y los estudios in vitro son un tema científico muy importante.

Introdução: as ftalocianinas são corantes à base de porfirinas. Eles têm muitas aplicações em diferentes campos, incluindo pesquisas biomédicas e químicas. Do ponto de vista químico, as ftalocianinas são compostos macrocíclicos tetraaza, que são constituídos principalmente por grupos isoindol que conferem aromaticidade e planaridade à estrutura das ftalocianinas. Ao contrário de outros tipos de compostos de porfirina, a estrutura da ftalocianina é capaz de quelar uma grande quantidade de metais, que mais frequentemente contribuem para sua enorme variedade de funções, incluindo geração de ROS, fluorescência, espectro de absorção e outros. Objetivo: avaliar alguns derivados de ftalocianinas graças às excelentes propriedades fotoquímicas e farmacêuticas que explicam a sua ampla utilização a nível clínico e médico. Metodologia: efetuamos uma busca minuciosa de trabalhos científicos relacionados ao assunto entre abril de 2020 e abril de 2021, a maioria deles redigidos na língua inglesa. Como resultado, podemos dizer que, para estudar as propriedades das ftalocianinas, o trabalho pode ser dividido em duas questões: síntese das ftalocianinas metalizadas e propriedades fotoquímicas e fotobiológicas. Resultados: as ftalocianinas têm muitas propriedades desejáveis para a pesquisa biomédica e farmacêutica. Pelas suas propriedades fotoquímicas e fotobiológicas, além da geração de ROS, as ftalocianinas são um dos ffotossensibilizantes mais amplamente utilizados na terapia fotodinàmica e processos fototóxicos. Eles também têm atividades antibacteriana, antiviral e anticàncer. Nesse sentido, a síntese de ftalocianina e os estudos in vitro são uma questão científica muito importante.

An in vitro study on the clearance effect of oxygen-releasing photodynamic therapy on Enterococcus faecalis in the root canal / 口腔疾病防治

Objective@#To investigate the clearance effect of photodynamic therapy (PDT) with an oxygen-releasing photosensitizer methylene blue (MB) formula on Enterococcus faecalis in the root canal.@*Methods @# Groups were divided into the MB group and oxygen release MB group. Samples in the MB group were mixed with 50 μmol/L MB solution, and samples in the oxygen release MB group were mixed with 50 μmol/L MB in oxygen release emulsion. N-acetyl-L-tryptophan amide (NATA) and 1,3-diphenylisobenzofuran (DPBF) were used to detect the oxidative activity and singlet oxygen generation of different formulas of MB (MB group, oxygen-releasing MB group), and the oxygen-releasing capacity of the oxygen-releasing photosensitizer formula was analyzed. The single root canal anterior teeth were collected, and the Enterococcus faecalis root canal infection model of isolated teeth was constructed. The distribution of Enterococcus faecalis in the root canal was observed by scanning electron microscopy. The isolated teeth with Enterococcus faecalis root canal infection were divided into three groups: the conventional root canal therapy group, MB-PDT therapy group, and oxygen-releasing MB-PDT therapy group, with 10 teeth in each group. Bacterial samples in the root canals of each group were obtained, the number of colonies was analyzed(CFU/mL) after 24 h of in vitro culture, and the clearance rate of Enterococcus faecalis in the root canal by photodynamic therapy was evaluated. The remaining isolated teeth with Enterococcus faecalis root canal infection were divided into 3 groups, with 5 samples in each group. Bacterial samples at a depth of 1 000 μm in the dentin tubules of the upper root, middle root and lower root segment were obtained and cultured in vitro for 24 h for calculations. The number of colonies (CFU/mL) was analyzed, and the clearance rate of Enterococcus faecalis in the dentin tubules of different segments of the root canals in each group was analyzed. @*Results @#The oxidation activity and singlet oxygen generation capacity in the oxygen-releasing MB group were stronger than those in the MB group. Scanning electron microscope detection showed that Enterococcus faecalis was distributed in dentinal tubules, indicating that the model of root canal infection in vitro was successfully constructed. The clearance rate of Enterococcus faecalis in the oxygen-releasing MB-PDT therapy group was higher than that in the conventional therapy group and the MB-PDT therapy group (P<0.05). Oxygen-releasing PDT significantly improved the bactericidal effect in the lower dentinal tubules, and the clearance rate of Enterococcus faecalis was better than in the other two groups (P<0.05).@*Conclusion@#Photodynamic therapy with the oxygen-releasing photosensitizer MB can achieve a better root canal bactericidal effect and can significantly improve the clearance effect of Enterococcus faecalis in the deep dentin of the lower root segment.

Research advances of photosensitizer in photodynamic therapy of glioblastoma / 药学学报

Glioblastoma is a malignant tumor in central nervous system, which has strong invasion, poor prognosis and short survival time. At present, the main treatment strategy of glioblastoma is surgical excision, supplemented by radiotherapy and chemotherapy. However, due to incomplete resection and high recurrence rate, it is urgent to find novel therapeutic method for glioblastoma. Photodynamic therapy, as a promising non-surgical treatment, provides a new strategy for postoperative adjuvant therapy of glioblastoma. This review summarizes the mechanism and clinical application of photodynamic therapy mediated by various photosensitizers in glioblastoma, in order to provide help for the treatment of glioblastoma.

Research progress on curcumin-mediated photodynamic therapy for oral infectious diseases / 口腔疾病防治

@#Curcumin is a natural medicine with a wide range of sources and low toxicity. It has antibacterial, antifungal, anti-inflammatory and other pharmacological effects. In recent years, curcumin has attracted much attention in the field of prevention and treatment of oral infectious diseases. Single curcumin is easily degraded during application and has poor water solubility and low bioavailability, but it can be used as a natural photosensitizer to mediate photodynamic treatment of oral infections. Photodynamic therapy has high antibacterial efficiency and can better protect the appearance and function of the affected area. This article reviews the research on curcumin-mediated photodynamic therapy for oral infectious diseases. As a natural photosensitizer, curcumin mediates photodynamic therapy and has shown good therapeutic effects against dental caries, endodontics, periodontitis, oral candidiasis and other oral infectious diseases by enhancing antibacterial ability, increasing the production of reactive oxygen species, and inhibiting the formation of biofilms. In-depth exploration of the mechanism of action of curcumin-mediated photodynamic therapy in different oral infectious diseases can provide new strategies for the prevention and treatment of oral infectious diseases.

Killing effects in vitro of a new photosensitizer black titanium dioxide-mediated photodynamics on prostate cancer cells / 肿瘤研究与临床

Objective:To investigate the killing effects in vitro of a new photosensitizer black titanium dioxide b-TP-700-mediated photodynamics on prostate cancer cell line PC-3 cells.Methods:The b-TP-700 was successfully prepared by using solid phase in situ thermal reduction method. PC-3 cells were treated with 31.25, 62.5, 125, 250, 500, 1 000 μg/ml b-TP-700 for 12, 24, 48 h. The cell activity was detected by using CCK-8 method, and the morphology of PC-3 cells was observed by using confocal fluorescence microscope, the toxicity of b-TP-700 to PC-3 cells was also judged. PC-3 cells were treated with different concentrations of b-TP-700 (31.25, 62.5, 125, 250, 500 μg/ml) and irradiated with laser (1 W/cm, 808 nm) for 1, 3, 5, 7 min. The cell activity was detected by using CCK-8 method. The production of reactive oxygen species in PC-3 cells cultured in 250 μg/ml b-TP-700 after laser irradiation for 5 min was detected by using confocal fluorescence microscopy. The non-laser irradiation cells were selected as the control group.Results:There were no statistically significant differences in cell activity of PC-3 cells treated with different concentrations of b-TP-700 for the same time ( F value was 1.26, 0.39 and 0.37, respectively; all P > 0.05). PC-3 cells were treated with 1 000 μg/ml b-TP-700 for 24 h, no obvious morphological changes and no obvious dead cells were observed under fluorescence microscope. When PC-3 cells were treated with the same concentration of b-TP-700, the activity of PC-3 cells was decreased with the extension of laser excitation time. Under the same laser excitation time, the activity of PC-3 cells was decreased with the increase of b-TP-700 concentration (all P < 0.05). Under laser irradiation, obvious green fluorescence could be detected in the PC-3 cells treated with 250 μg/ml b-TP-700, while almost no green fluorescence could be observed in the control group. Conclusions:A new photosensitizer b-TP-700 has the good reactive oxygen generation ability. b-TP-700-mediated photodynamics show obvious killing effects on prostate cancer PC-3 cells in vitro, which is expected to be a new method for the treatment of prostate cancer.

Anti-tumor nanoscale drug delivery systems based on photodynamic therapy / 药学学报

Photodynamic therapy (PDT) is a therapeutic strategy by which photosensitizers are excited by specific light irradiation to produce singlet oxygen for killing the surrounding cells. The advantages of PDT include weak invasion, slight side effect, and low resistance. The advantages of nanoscale drug delivery systems (DDS) include tumor-targeting, sustained release, and environmental-sensitivity. The combination of PDT and nanoscale DDS would likely lead to tumor targeting of photosensitizers and enhance their antitumor effectiveness. This review discusses the mechanism of PDT, photosensitizer-loaded nanoscale formulations, the combination of PDT and other antitumor therapies, and summarizes the applications and prospects of anti-tumor nanoscale DDS based on PDT. This review is a useful reference for its clinical application.

A smart MnO

The combination of chemotherapy and photodynamic therapy provides a promising approach for enhanced tumor eradication by overcoming the limitations of each individual therapeutic modality. However, tumor is pathologically featured with extreme hypoxia together with the adaptable overexpression of anti-oxidants, such as glutathione (GSH), which greatly restricts the therapeutic efficiency. Here, a combinatorial strategy was designed to simultaneously relieve tumor hypoxia by self-oxygenation and reduce intracellular GSH level to sensitize chemo-photodynamic therapy. In our system, a novel multi-functional nanosystem based on MnO

Research progress on the application of photodynamic therapy in periodontal treatment / 口腔疾病防治

@#Periodontitis is a chronic inflammatory disease that is initiated by bacteria. Pathogens and their virulence factors alter normal cellular metabolic activity and deteriorate periodontal microconditions. Owing to the complexity of tooth structure and the limitation of conventional treatment, we may not live up to all patients’ expectations, especially those with grade C and stage Ⅲ or Ⅳ periodontitis. With the advantages of bactericidal effects, high safety, inhibition of bacterial drug resistance and promotion of tissue healing, photodynamic therapy （PDT） seems to be an ideal technology in periodontal treatment. However, it cannot remove subgingival stones and still cannot replace mechanical treatment to preliminarily control periodontal inflammation. Therefore, near-infrared low-energy light combined with traditional photosensitizers is mostly used in clinical periodontal adjuvant treatment. In periodontal maintenance treatment on a regular basis, a single application can also reduce the sensitivity of patients and effectively control plaque, but its effect will be affected by the degree of periodontal inflammation, the concentration and type of photosensitizer, the energy of the light source, etc. With the further development of material science, the performance of photosensitizers to accelerate oxides and target bacteria will be optimized. In the future, parameters of PDT need to be designed in large-scale studies in accord with different stages and grades of periodontitis.

Progress in the photodynamic therapy treatment of Leishmaniasis

Leishmaniasis is a serious and endemic infectious disease that has been reported in more than 90 countries and territories. The classical treatment presents a series of problems ranging from difficulty in administration, development of resistance, and a series of side effects. Photodynamic therapy (PDT) has already shown great potential for use as a treatment for leishmaniasis that is effective and non-invasive, with very minor side effects. PDT can also be inexpensive and easy to administer. In this review, we will report the most recent developments in the field, starting with the chemical diversity of photosensitizers, highlighting important mechanistic aspects, and noting information that may assist in designing and developing new and promising photosensitizer molecules.

Irradiation Time of Photodynamic Therapy to the Number of Lactobacillus acidophilus

ABSTRACT@#Lactobacillus acidophilus (L. acidophilus) is one of the etiological agents for dental caries and dominant in the deep carious lesion. L. acidophilus has also been identified in persistent root canal infection and also related to the failure of endodontic treatment. Photodynamic therapy is a therapeutic process involving the combination of a nontoxic photosensitizer and a light source. The excited photosensitizer reacts with reactive oxygen species (ROS), which induce injury and death of the microorganism. This study aimed to prove the effect of irradiation time of photodynamic therapy to the number of L. acidophilus. Forty-two Eppendorf tubes were treated with 0.5 ml L. acidophilus distributed into seven groups. Group 1 as the control group received no treatment. Groups 2, 3, 4, 5, 6 and 7 were treated with a combination of 0.5 ml toluidine blue O (TBO) as a photosensitizer and 630 nm photoactivated (Fotosan®) exposure time for 10, 20, 30, 40, 50 and 60 sec. Then, all were stored in an incubator of 37ºC for 48 h. Later, the colony-forming unit (CFU) was counted for each group. There were significant differences in the number of L. acidophilus in CFU of the various irradiation times. The longer the photodynamic therapy irradiation was, the lesser the number of live L. acidophilus became. At 50 sec and 60 sec irradiation, none of the L. acidophilus was found alive.

Oxidative foliar photo-necrosis produced by the bacteria Pseudomonas cedrina

BACKGROUND: Although bioactive metabolites capable of causing oxidative photo-necrosis in plant tissues have been identified in fungi, little is known about this type of mechanism in bacteria. These metabolites act as photosensitizers that generate reactive oxygen species (ROS) capable of causing damage to cells. In addition, these metabolites can pass into an energetically excited state when they receive some luminous stimulus, a condition in which they interact with other molecules present in the environment, such as molecular oxygen (O2), also known as triplet oxygen (3 O2), generating ROS. RESULTS: The suspension of the bacterial culture of Pseudomonas cedrina was shown to produce foliar necrosis in papaya leaves (Carica papaya L.) only in the presence of sunlight, which is evidence of photosensitizing mechanisms that generate singlet oxygen (1 O2). From the chemical study of extracts obtained from this bacteria, 3-(4-(2-carboxipropyl) phenyl) but-2-enoic acid (1) was isolated. This compound, in the presence of light and triplet oxygen (3 O2), was able to oxidize ergosterol to its peroxide, since it acted as a photosensitizer producing 1 O2, with which it was corroborated that a photosensitization reaction occurs, mechanism by which this bacterium could prove to cause oxidative foliar photo-necrosis. CONCLUSIONS: P. cedrina was able to induce oxidative foliar photo-necrosis because of its potential ability to produce photosensitizing metabolites that generate singlet oxygen in the plants it colonizes. Based on the above, it can be proposed that some bacteria can cause oxidative foliar photo-necrosis as an important mechanism in the pathogenesis of host species.

Design, synthesis and antitumor activities of chlorin p6 ether derivatives as photosensitizer for photodynamic therapy / 药学实践杂志

Objective To designe, synthesize a series of chlorin p6 ether photosensitizers and preliminarily investigate their photodynamic antitumor activity based on previous research results that alkoxyl ether derivatives of 3-vinyl on chlorin f exhibited stronger photosensitive antitumor activity than parent compound. Methods Purpurin-18 (4) was obtained by oxidative degradation with air and alkali on pheophorbide a (5) which was prepared through acid hydrolysis of chlorophyll a from crude chlorophyll extracts in Chinese traditional herb named Silkworm excrement. Then, chlorin p6 trimethylester (2) were formed via basic hydrolysis of internal anhydride ring for lead compound 3 and following immediately methylation with CH2N2. The intermediate 2 reacted with 33% HBr, following nucleophilic substitution with various alkoxyl alcohol to get six title compounds (1). All title compounds were subjected to photodynamic antitumor activity screening for melanoma B16-F10 cell in vitro. Results All title compounds showed much higher phototoxicity against melanoma B16-F10 cells than talaporfin and verteporfin. Their structures were confirmed by 1H-NMR, 13C-NMR, ESI-MS and ESI-HRMS spectra. Conclusion Chlorin p6 ether compounds were promising candidate photosensitizers for PDT applications due to theirs high dark toxicity/phototoxicity ratio and excellent phototoxicity, which were worthy of further research and development.

Experimental study of photodynamic therapy using a new photosensitizer BF01 for human liver cancer / 药学学报

We study here in vitro cytotoxicity, in vivo tumor inhibition and the mechanism on photodynamic therapy (PDT) of photosensitizer BF01 using human hepatocellular carcinoma cell line BEL-7402. CCK-8 method was used to detect the inhibition rate and IC50 in BEL-7402 cells on the same laser intensity with varying concentrations (0, 0.8, 1.6, 3.2, 6.4 μmol·L-1) of photosensitizer BF01. Cell death mode of BEL-7402 was detected by flow cytometry, with apoptotic characteristics observed by DAPI staining, and the subcellular localization of reactive oxygen was observed using photodynamic detection and confocal microscopy. The cell model of human liver cancer in nude mice was established, tumor growth curve was drawn, and the therapeutic effect of BF01 was determined. The animal experimentation was approved by East China University of Science and Technology Ethics Committee. The results indicated that BF01 PDT treatment can clearly inhibit BEL-7402 tumor cell proliferation, with the killing rate of 86% at the concentration of 6.4 μmol·L-1 of BF01, and half lethal concentration IC50 value of 2.46 μmol·L-1. DAPI stained nuclei shows the characteristics of advanced stage apoptosis, whereas reactive oxygen species level in the mitochondria increased with increasing drug concentration. In vivo experiments showed that photosensitizer BF01 mediated photodynamic therapy of liver cancer cells and inhibited tumor growth in mice. Therefore, the new BF01 photosensitizer has a potential for development into future clinic application.

Experimental study of a novel photosensitizer mediated photodynamic therapy on resistant gastric cancer / 中国药理学通报

Aim To investigate the therapeutic efficacy of DTP-mediated photodynamic therapy (PDT) on SGC7901/VCR human vincristine ( VCR )-resistant gastric cancer cells, and to reveal the relationship between DTP-PDT and P-gp. Methods MTT assay was employed to evaluate the cytotoxicity of DTP-PDT and combination treatment with DTP-PDT and VCR. A SGC7901/VCR-bearing nude mouse model was established, and the tumor volume was measured to draw the growth curve. Cell apoptosis was detected by flow cytometry, and the yield of intracellular singlet oxygen (O2) was determined after DTP-PDT. The expression of MDR1 mRNA and P-gp was determined by qPCR and flow cytometry, respectively. Results DTP-PDT demonstrated significant cytotoxicity on SGC7901/VCR cells and the nude mice transplanted tumor. DTP-PDT could induce the apoptosis of SGC7901/VCR cells and the generation of intracellular O2. DTP-PDT could inhibit the expression of MDR1 mRNA and P-gp, which could be reduced by a-tocopherol. Combined treatment with DTP-PDT and VCR demonstrated synergistic efficacy on resistant cells, which could be reduced by or-tocopherol. Conclusions O2 generated by DTP-me-diated PDT could inhibit the growth of SGC7901/VCR cells and induce cell apoptosis. Meanwhile, it inhibits the over-expression of P-gp on cell membranes, leading to reduced efflux of VCR and synergistic efficacy with DTP-PDT and VCR eventually.

Applications of Ru(II)-polypyridyl complexes in two-photon photodynamic therapy / 药学学报

Photodynamic therapy (PDT) has emerged as a more effective and promising treatment towards cancer therapy. PDT is a minimally invasive and spatially selective medical technique to destroy cancer cells without drug resistance, which has been increasingly applied in the clinical praxis alongside surgery, chemotherapy and radiotherapy. However, traditional PDTs use a high energy one-photon laser beam, which is far from the efficient optical window of mammalian tissue (650−950 nm). Moreover, it has great limitations in the depth of penetration, and induces the undesired light toxicity. The development of photosensitizers has always been a bottleneck to the effective application of PDT in clinical practice. From the first generation of hematoporphyrin derivatives to the third-generation photosensitizers with tumor targeting ability, they meet the urgent clinical needs to some extent, but they still can not satisfy the requirements of two-photon PDT. Therefore, the development of photosensitizers, which are capable of two-photon activated PDT, has become a promising approach. Among the various two-photon absorption photosensitizers, ruthenium (Ⅱ) polypyridyl complexes have been recognized as excellent candidates due to their attractive photophysical properties. This review is prepared to summarize the recent achievements in the application of ruthenium (Ⅱ) polypyridyl complexes as photosensitizers for two-photon PDT, as well as to provide guidance for the design of two-photon activated photosensitizers in future research.